Aspirin for in vitro fertilisation.

BACKGROUND: Aspirin is used to improve the outcome in women undergoing in vitro fertilisation despite inconsistent evidence of its efficacy. The most appropriate time to commence aspirin therapy and the length of treatment required are also still to be determined. This is an update of the review first published in 2007. OBJECTIVES: To determine the effectiveness and safety of aspirin for improving the outcome of in vitro fertilisation and intracytoplasmic sperm injection treatment cycles. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library January 2011), MEDLINE (1966 to January 2011) and EMBASE (1980 to January 2011) databases. We used the research terms: "(aspirin OR acetylsalicylic acid) AND (in-vitro fertilisation OR intracytoplasmic sperm injection)", combined with the Cochrane Menstrual Disorders and Subfertility Group's search strategy, in order to identify randomised controlled trials on aspirin for women undergoing in vitro fertilisation. SELECTION CRITERIA: Randomised controlled trials. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies to include in the review, extracted data and assessed trial quality. MAIN RESULTS: The searches identified 13 trials which were eligible for inclusion in the review, including a total of 2653 participants. No significant differences were found between the treatment and control groups for any of the outcomes assessed. No significant differences were found in the meta-analysis of studies investigating the effect of aspirin compared with control on live birth rate (RR 0.91, 95% CI 0.72 to 1.15; three studies and 1053 participants), clinical pregnancy rate (RR 1.03, 95% CI 0.91 to 1.17; 10 studies and 2142 participants), ectopic and miscarriage rates (RR 1.86, 95% CI 0.75 to 4.63; RR 1.10, 95% CI 0.68 to 1.77) respectively (three and five studies involving 1135 and 1497 participants). AUTHORS' CONCLUSIONS: Use of aspirin for women undergoing in vitro fertilisation cannot be recommended due to lack of evidence from the current trial data. Adequately powered trials are needed. It was proposed in the initial version of this review that a sample size of 350 women in each group would be required in order to demonstrate a 10% improvement from the use of aspirin, with 80% power at the 5% significance level. Until such evidence is available, this treatment can not be recommended.

Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction.

BACKGROUND: Gonadotrophin-releasing hormone agonists (GnRHa) are used in assisted reproduction technology (ART) cycles to prevent a luteinizing hormone surge. Various protocols have been described in the literature, such as long protocols (continuous and stop or reduce dose, long luteal, or long follicular protocol); short protocols and ultrashort protocols. OBJECTIVES: To determine the most effective GnRHa protocol as an adjuvant to gonadotrophins in ART cycles. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINHAHL and PsycINFO. Reference lists of relevant articles were also searched. All the searches were updated to August 2010. SELECTION CRITERIA: Only randomised controlled trials comparing any two protocols of GnRHa in in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) cycles were included. DATA COLLECTION AND ANALYSIS: The primary outcome measure was live births per women. Secondary outcome measures were pregnancy rate, ongoing pregnancy rate, number of oocytes retrieved and amount of gonadotrophins used. Data were independently extracted in 2 x 2 tables by two authors. Odds ratios (OR) with 95% confidence intervals (CI) were calculated after verifying the presence of homogeneity of treatment effect across all trials. For continuous variables mean differences (MD) were calculated. MAIN RESULTS: Of 29 included studies, 17 compared long with short protocols; two compared long with ultrashort protocols; four compared a follicular versus luteal start of GnRHa; three compared continuation versus stopping the GnRHa at the start of stimulation; three compared continuation of the same dose versus reduced dose of GnRHa and one compared a short versus short stop protocol.There was no evidence of a difference in the live birth rate but this outcome was only reported by three studies.There was evidence of a significant increase in clinical pregnancy rate (OR 1.50, 95% CI 1.16 to 1.93) in a long protocol when compared to a short protocol. That is there is a 50% increase in chance of achieving pregnancy if a long protocol is used as compared to a short protocol, although this difference could range from 16% to 93% increased chance of pregnancy. This difference did not persist when the meta-analysis was done only on the studies with adequate randomisation (OR 1.38, 95% CI 0.93 to 2.05).There was evidence of an increased number of oocytes (MD 1.61, 95% CI 0.18 to 3.04) obtained when a long protocol was used as compared to a short protocol. That is there is a 60% increase in the number of oocytes retrieved when a long protocol is used as compared to a short protocol, although this difference could range from 18% to 304% more oocytes.There was evidence of an increase (MD 12.90, 95% CI 3.29 to 22.51) in the requirement for gonadotrophins in long as compared to short protocols. That is approximately 12.9 more ampoules of gonadotrophins were consumed when a long protocol was used as compared to a short protocol. This difference could range from 3.29 to 22.51 more gonadotrophin ampoules.There was no evidence of a difference in any of the outcome measures for luteal versus follicular start of GnRHa and stopping versus continuation of GnRHa at the start of stimulation. AUTHORS' CONCLUSIONS: The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

In vitro maturation in sub fertile women with polycystic ovarian syndrome undergoing assisted reproduction.

BACKGROUND: Polycystic ovarian syndrome (PCOS) occurs in 4% to 7% of all women of reproductive age and 20% of women presenting with sub-fertility. A significant proportion of these women will ultimately need assisted reproductive techniques (ART). In women with PCOS, the supra-physiological doses of gonadotrophins used for controlled ovarian hyperstimulation (COH) often result in an exaggerated ovarian response characterised by the development of a large cohort of follicles of uneven quality, retrieval of immature oocytes, and increased risk of ovarian hyperstimulation syndrome. A potentially useful intervention for women with PCOS-related infertility involves earlier retrieval of immature oocytes followed by in vitro maturation (IVM). OBJECTIVES: To compare live birth rates per woman following in vitro maturation (IVM) with conventional in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) for women with PCOS undergoing ART. SEARCH STRATEGY: We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials for any relevant trials from the title, abstract, or keyword sections. Following a search of electronic databases (MEDLINE in all languages) using Ovid software we also performed a manual search of the references of all retrieved articles, sought unpublished papers and abstracts submitted to international conferences, and contacted experts. In addition, we searched the National Institute of Clinical Excellence fertility assessment and treatment guidelines (NICE 2004) and handsearched reference lists of relevant systematic reviews and randomised trials. SELECTION CRITERIA: All randomised trials on the intention to perform IVM before IVF or ICSI and conventional IVF or ICSI for sub-fertile women with PCOS. DATA COLLECTION AND ANALYSIS: We identified no studies that met the inclusion criteria. MAIN RESULTS: There were no trials suitable for inclusion in the review. AUTHORS' CONCLUSIONS: There are no randomised controlled trials upon which to base any practice recommendations regarding IVM before IVF or ICSI for women with PCOS. There is an urgent need for randomised trials in this field.